Variant chr2-73221881-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006062.3(SMYD5):c.593C>T(p.Ala198Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000992 in 1,613,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SMYD5
NM_006062.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.58

Variant links:

Genes affected

SMYD5 (HGNC:16258): (SMYD family member 5) Predicted to enable histone methyltransferase activity (H4-K20 specific). Involved in negative regulation of transposition and regulation of stem cell differentiation. [provided by Alliance of Genome Resources, Apr 2022]

SMYD5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35144728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMYD5	NM_006062.3 linkuse as main transcript	c.593C>T	p.Ala198Val	missense_variant	6/13	ENST00000389501.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SMYD5	ENST00000389501.9 linkuse as main transcript	c.593C>T	p.Ala198Val	missense_variant	6/13	1	NM_006062.3	P1
SMYD5	ENST00000474652.1 linkuse as main transcript	n.712C>T		non_coding_transcript_exon_variant	6/6	5
SMYD5	ENST00000477038.1 linkuse as main transcript	n.115C>T		non_coding_transcript_exon_variant	2/4	5
SMYD5	ENST00000258100.8 linkuse as main transcript	c.*361C>T		3_prime_UTR_variant, NMD_transcript_variant	6/8	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000557

AC:

AN:

251482

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461524

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.593C>T (p.A198V) alteration is located in exon 6 (coding exon 6) of the SMYD5 gene. This alteration results from a C to T substitution at nucleotide position 593, causing the alanine (A) at amino acid position 198 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.014

Eigen

Benign

-0.058

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.012

MetaRNN

Benign

0.35

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.18

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.49

REVEL

Benign

0.12

Sift

Benign

0.65

Sift4G

Benign

1.0

Polyphen

0.051

Vest4

0.78

MutPred

0.31

Gain of helix (P = 0.0425);

MVP

0.78

MPC

0.38

ClinPred

0.078

GERP RS

5.5

Varity_R

0.12

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over